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The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro.

Carlsson JA, Wold AE, Sandberg AS, Östman SM - PLoS ONE (2015)

Bottom Line: Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells.Fatty acids were taken up by the DCs, as shown by gas chromatography analysis.However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violet low) and expressed CD69 or CD25, while more were necrotic (7AAD+).

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

ABSTRACT
Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 μM fatty acids; α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violet low) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNγ. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells.

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Soluble CD83 (sCD83) and prostaglandin E2 (PGE2) in dendritic cell (DC) culture supernatant.(A) Levels of sCD83 (pg/ml). (B) Levels of PGE2 (pg/ml). DC cultures were supplemented with fatty acids (50 μM); arachidonic acid (AA), docosahexaenoic acid (DHA), oleic acid (OA) or ethanol (Ctrl) for 3 days and supernatants analyzed by ELISA. Black dots denote samples supplemented with fatty acid while white dots with black borders denote control (ethanol only). Horizontal solid black lines show median value. The median from the control group has been extended with a dotted line for easy comparison to the other groups. Statistical mean difference was compared to the control group. Data are representative of one experiment. The limit of detection (LoD) is shown with dashed black lines. p-values: * <0.05, ** <0.01, *** <0.001.
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pone.0143741.g005: Soluble CD83 (sCD83) and prostaglandin E2 (PGE2) in dendritic cell (DC) culture supernatant.(A) Levels of sCD83 (pg/ml). (B) Levels of PGE2 (pg/ml). DC cultures were supplemented with fatty acids (50 μM); arachidonic acid (AA), docosahexaenoic acid (DHA), oleic acid (OA) or ethanol (Ctrl) for 3 days and supernatants analyzed by ELISA. Black dots denote samples supplemented with fatty acid while white dots with black borders denote control (ethanol only). Horizontal solid black lines show median value. The median from the control group has been extended with a dotted line for easy comparison to the other groups. Statistical mean difference was compared to the control group. Data are representative of one experiment. The limit of detection (LoD) is shown with dashed black lines. p-values: * <0.05, ** <0.01, *** <0.001.

Mentions: We also measured soluble factors in the supernatant of DC cultures stimulated with the fatty acids arachidonic acid, DHA or oleic acid for 72 hours. We observed high levels of PGE2, >2 pg/ml, in DC cultures stimulated with arachidonic acid whereas <0.2 pg/ml of PGE2 was found with the other stimuli (Fig 5B). Since we observed an upregulation of CD83 expression on DCs supplemented with arachidonic acid and DHA we also measured soluble CD83 (sCD83) in the supernatant. Only low levels of sCD83 was detected, and without differences between the groups (Fig 5A). The levels of IL-10, IL-12 p70, and IFNγ were below detection limit while TGF-β1 levels were in pair with the levels in fresh complete IMDM (containing fetal bovine serum), with no differences between the groups.


The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro.

Carlsson JA, Wold AE, Sandberg AS, Östman SM - PLoS ONE (2015)

Soluble CD83 (sCD83) and prostaglandin E2 (PGE2) in dendritic cell (DC) culture supernatant.(A) Levels of sCD83 (pg/ml). (B) Levels of PGE2 (pg/ml). DC cultures were supplemented with fatty acids (50 μM); arachidonic acid (AA), docosahexaenoic acid (DHA), oleic acid (OA) or ethanol (Ctrl) for 3 days and supernatants analyzed by ELISA. Black dots denote samples supplemented with fatty acid while white dots with black borders denote control (ethanol only). Horizontal solid black lines show median value. The median from the control group has been extended with a dotted line for easy comparison to the other groups. Statistical mean difference was compared to the control group. Data are representative of one experiment. The limit of detection (LoD) is shown with dashed black lines. p-values: * <0.05, ** <0.01, *** <0.001.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4664484&req=5

pone.0143741.g005: Soluble CD83 (sCD83) and prostaglandin E2 (PGE2) in dendritic cell (DC) culture supernatant.(A) Levels of sCD83 (pg/ml). (B) Levels of PGE2 (pg/ml). DC cultures were supplemented with fatty acids (50 μM); arachidonic acid (AA), docosahexaenoic acid (DHA), oleic acid (OA) or ethanol (Ctrl) for 3 days and supernatants analyzed by ELISA. Black dots denote samples supplemented with fatty acid while white dots with black borders denote control (ethanol only). Horizontal solid black lines show median value. The median from the control group has been extended with a dotted line for easy comparison to the other groups. Statistical mean difference was compared to the control group. Data are representative of one experiment. The limit of detection (LoD) is shown with dashed black lines. p-values: * <0.05, ** <0.01, *** <0.001.
Mentions: We also measured soluble factors in the supernatant of DC cultures stimulated with the fatty acids arachidonic acid, DHA or oleic acid for 72 hours. We observed high levels of PGE2, >2 pg/ml, in DC cultures stimulated with arachidonic acid whereas <0.2 pg/ml of PGE2 was found with the other stimuli (Fig 5B). Since we observed an upregulation of CD83 expression on DCs supplemented with arachidonic acid and DHA we also measured soluble CD83 (sCD83) in the supernatant. Only low levels of sCD83 was detected, and without differences between the groups (Fig 5A). The levels of IL-10, IL-12 p70, and IFNγ were below detection limit while TGF-β1 levels were in pair with the levels in fresh complete IMDM (containing fetal bovine serum), with no differences between the groups.

Bottom Line: Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells.Fatty acids were taken up by the DCs, as shown by gas chromatography analysis.However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violet low) and expressed CD69 or CD25, while more were necrotic (7AAD+).

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

ABSTRACT
Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 μM fatty acids; α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violet low) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNγ. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells.

Show MeSH
Related in: MedlinePlus